Cadmium and lead are agents which produce a variety of adverse physiological effects including alterations of immune functions. However, the full spectrum of their activity has not yet been defined and the mechanisms which they produce their effects are unknown. It is known that the distribution and retention of these metals differs in newborns and adults, but the consequences of these differences on the development of the immune system during the perinatal period are unknown. In this application we propose to compare the effects of lead and cadmium on both cellular and humoral immune responses in adult and neonatal mice. We will determine critical dose-response relationship by measuring discrete immune functions, i.e., cellular and humoral responses, and by measuring metal content in various lymphoid and non-lymphoid tissue. Within these studies, we will examine metal distribution in functionally distinct subpopulations of lymphocytes. In each of these systems we will study possible interactions between cadmium or lead on zinc metabolism in order to determine if the toxic effects of these metals are related to a disruption of essential trace metal metabolism. Since the protein, metallothionein, is centrally involved in the metabolism of both zinc and cadmium, we will measure metallothionein levels in various tissues and cell types. Finally, because bacterial endotoxins are known to produce a variety of effects on immune function and since some effects of endotoxin are potentiated by both cadmium and lead, we will study possible roles of endotoxin on immunomodulation in metal treated mice.